Role of Sirolimus in Treatment of Microcystic , Mixed Lymphatic and Vascular Malformations

Lympho-vascular malformations result from errors in embryologic vasculogenesis involving capillaries, veins, arteries, lymphatics, or a combination of these. Infantile haemangiomas & Vascular malformations like : Capillary malformations & Venous malformations : they increase in size and never regress on their own. & They are generally present at birth, they enlarge in response to infection, hormonal changes or trauma . Lymphatic malformations can be classified into macrocystic (cyst diameter >1cm), microcystic (cyst diameter <1 cm), or mixed , in macrocystic lymphatic malformations, surgery and sclerotherapy are effective . Surgery of microcystic lymphatic malformations remains challenging due to their infiltrative nature & Sclerotherapy is often impossible. As especially large microcystic and mixed malformations are still a therapeutic challenge, pharmaceutical treatment as sirolimus is used in last years as main line of treatment with great efficacy.

Study Overview

• Status: Recruiting
• Conditions: Vascular Malformations; Microcystic Lymphatic Malformation; Combined Vascular Malformation
• Intervention / Treatment: Drug: Sirolimus 1Mg Oral Tablet

Detailed Description

Lympho-vascular malformations result from errors in embryologic vasculogenesis involving capillaries, veins, arteries, lymphatics, or a combination of these. Infantile haemangiomas & Vascular malformations like : Capillary malformations & Venous malformations : they increase in size and never regress on their own. & They are generally present at birth, they enlarge in response to infection, hormonal changes or trauma . Lymphatic malformations can be classified into macrocystic (cyst diameter >1cm), microcystic (cyst diameter <1 cm), or mixed , in macrocystic lymphatic malformations, surgery and sclerotherapy are effective . Surgery of microcystic lymphatic malformations remains challenging due to their infiltrative nature & Sclerotherapy is often impossible. As especially large microcystic and mixed malformations are still a therapeutic challenge, pharmaceutical treatment as sirolimus is used in last years as main line of treatment with great efficacy. Sirolimus is a natural macrolide isolated from a bacteria strain of the Streptomyces genus & Streptomyces hygroscopicus . It was initially used as an antibiotic and antifungal agent, subsequent studies have revealed impressive cytostatic, antiproliferative, and immunosuppressive properties . Sirolimus not only prevents the growth of abnormal lymphatics but also induces the partial regression of lesions, without apparent effects on normal lymphatics .

• Study Type: Observational
• Enrollment (Estimated): 10

Contacts and Locations

• Study Contact: Name: Tarek A Abd elsalam, resident; Phone Number: 01064411709; Email: tarikahmed@med.sohag.eg
• Study Contact Backup: Name: Mohamed yousef, Ass. Prof.

Study Locations

• Egypt
  • Sohag, Egypt
    • Recruiting
    • Sohag University Hospital
    • Contact: Magdy M Amin, professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

• from age 6 months to 12 years , not before 6 months to complete their vaccination program & maturation of hepatic enzymes .
• Patients diagnosed with microcystic & mixed Lymphatic malformations .
• After failure of other lines of treatment as regard propranolol , steroid for infantile haemangiomas & Vascular malformations and lymphovascular malformations .
• After failure of surgical excision & injection of bleomycin of Lympho-vascular malformations

Description

Inclusion Criteria:

• from age 6 months to 12 years , not before 6 months to complete their vaccination program & maturation of hepatic enzymes .
• Patients diagnosed with microcystic & mixed Lymphatic malformations .
• After failure of other lines of treatment as regard propranolol , steroid for infantile haemangiomas & Vascular malformations and lymphovascular malformations .
• After failure of surgical excision & injection of bleomycin of Lympho-vascular malformations

Exclusion Criteria:

• Macrocystic Lymphatic malformations & high flow vascular malformations like arterio-venous malformations .
• An active infection that requires systemic treatment during the attack .
• Side effects of the drug as ( history of an allergic reaction to sirolimus or patients who develop severe allergic reaction to drug during treatment , hyperlipidemia , leucopenia , etc… )
• Chronic liver or kidney disease or on chronic drug treatment as (steroids, interferon or chemotherapeutic agents) .
• An immunodeficiency condition such as a human immunodeficiency viral infection or primary immunodeficiency disease.
• Patients who received drug less than 6 months duration .

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
group A; microcystic & mixed lymphatic malformation	Drug: Sirolimus 1Mg Oral Tablet; patients with Microcystic , Mixed Lymphatic and Vascular Malformations will be given sirolimus 1 mg oral tab for 3-6 months with follow up of lesion size by clinical exam & ultrasound & MRI to compare lesion size before & after use of the drug with observation of potential side effects & after exclusion of it before use of the drug
group B; vascular malformation	Drug: Sirolimus 1Mg Oral Tablet; patients with Microcystic , Mixed Lymphatic and Vascular Malformations will be given sirolimus 1 mg oral tab for 3-6 months with follow up of lesion size by clinical exam & ultrasound & MRI to compare lesion size before & after use of the drug with observation of potential side effects & after exclusion of it before use of the drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes in size of the lesion	efficacy of sirolimus in decreasing size of the lesion over time , by clinical exam of size lesion & measurement of size of leesion by ultrasound & MRI	1 year

Collaborators and Investigators

• Sponsor: Sohag University

Publications and helpful links

General Publications

• Sadick M, Muller-Wille R, Wildgruber M, Wohlgemuth WA. Vascular Anomalies (Part I): Classification and Diagnostics of Vascular Anomalies. Rofo. 2018 Sep;190(9):825-835. doi: 10.1055/a-0620-8925. Epub 2018 Jun 6.
• Vlahovic AM, Vlahovic NS, Haxhija EQ. Sirolimus for the Treatment of a Massive Capillary-Lymphatico-Venous Malformation: A Case Report. Pediatrics. 2015 Aug;136(2):e513-6. doi: 10.1542/peds.2014-3469. Epub 2015 Jul 6.
• Muller-Wille R, Wildgruber M, Sadick M, Wohlgemuth WA. Vascular Anomalies (Part II): Interventional Therapy of Peripheral Vascular Malformations. Rofo. 2018 Feb 7. doi: 10.1055/s-0044-101266. Online ahead of print.
• Adams DM, Wentzel MS. The role of the hematologist/oncologist in the care of patients with vascular anomalies. Pediatr Clin North Am. 2008 Apr;55(2):339-55, viii. doi: 10.1016/j.pcl.2008.01.007.

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2023
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: November 29, 2023
• First Submitted That Met QC Criteria: November 29, 2023
• First Posted (Actual): December 7, 2023

Study Record Updates

• Last Update Posted (Estimated): December 15, 2023
• Last Update Submitted That Met QC Criteria: December 8, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphatic Diseases; Cardiovascular Abnormalities; Lymphatic Vessel Tumors; Congenital Abnormalities; Vascular Malformations; Lymphangioma; Lymphatic Abnormalities; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: soh-Med-23-11-16MS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No